tbuckley/cabot-search huggingface dataset:
D-dimer as a predictive biomarker of response to chemotherapy in patients with metastatic breast cancer.
Authors: Lubana Alkhoder, Sulaf Alwassouf, Maher Salamoon, Maher Saifo
Journal: Journal of Clinical Oncology (2023)

e13000 Background: Tumor-induced coagulation is considerably observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression, and metastasis, by creating a proliferative and proangiogenic microenvironment. Therefore , D-dimer, a fibrin degradation product, correlates with tumor prognosis in several cancer types. This study aims to investigate whether D-dimer levels can be a predictive and monitoring indicator for chemotherapy response in metastatic breast cancer (MBC) patients. Methods: This study included two groups, 76 patients diagnosed with metastatic breast carcinoma, and 25 with early breast carcinoma as a control group. Plasma D-dimer levels were measured prospectively before chemotherapy initiation, and after the fourth treatment cycle in MBC patients. The levels of D-dimer before chemotherapy (D0) were analyzed using receiver operating characteristic (ROC) curves to determine the optimal cutoff baseline values of D0, and to evaluate their discriminatory abilities in predicting response to chemotherapy. Results: In the preliminary response evaluation, the mean level of D-dimer significantly decreased by 2.74 μg/ml in patients with partial response, and by 2.17 μg/ml in patients with stable disease. In the progression disease group, a considerable increase was seen in D-dimer levels by 2.16 μg/ml. Analysis of ROC curves showed that D-dimer levels at D0 could discriminate the response to chemotherapy, whereas the progressive disease rate correlated with higher levels of D-dimer (&gt;1.055 μg/ml; P= 0.000). Conclusions: D-dimer level in plasma is a useful predictive and monitoring marker of response to chemotherapy in metastatic breast cancer.
Machine learning prediction of patient-reported outcomes associated with systemic therapy from medical records.
Authors: Frank Po-Yen Lin, Anthony M. Joshua, Richard J. Epstein
Journal: Journal of Clinical Oncology (2023)

e13564 Background: Measures of patient-reported outcome (PRO) are important metrics in cancer care. However, PROs are poorly captured in routine practice, and data collection may incur undue burden on patients. It remains unclear if electronic medical records (EMR) contain sufficient information to dynamically monitor PROs in patients undergoing intensive systemic therapy. Methods: Over a 6 week period, consecutive patients attending an outpatient chemotherapy unit completed two questionnaires (EORTC QLQ-C30 and NCI PRO-CTCAE) at each visit. The corresponding EMR, authored by oncologists and allied health providers, were extracted up to 4 weeks prior to the questionnaire date. Random forest algorithm was used to predict each dichotomized PRO class using bag-of- n-grams extracted from the text. The classification performance was assessed by 8-fold cross-validation, using the area under receiver operating characteristic curve (AUC) as the metric. This study is part of the ePERSIST (electronic phenotyping, event retrieval, and case summarisation in solid tumours) project, exploring methods for extracting structured variables from EMR to support oncology research. Results: 115 patients (157 visits to the chemotherapy unit) completed up to 6 sets of questionnaires each. Overall, the median quality-of-life (QOL) score of QLQ-C30, QL2, was 67 (IQR 50 to 83). Machine learning predicted low QL2 score with mean AUC of 0.710 (95% CI 0.630 to 0.791). At the Bonferroni threshold of 0.00025, machine learning significantly predicted several components of QLQ-C30: PF2 (mean AUC 0.722, 0.633 to 0.812), AP (0.725, 0.630 to 0.819), CO (0.686, 0.607 to 0.764), FI (0.677, 0.598 to 0.755), PA (0.696, 0.603 to 0.787), FA (0.686, 0.584 to 0.787), and RF2 (0.717, 0.595 to 0.839). Conversely, EMR could only be used to significantly predict 4 of 13 PRO-CTCAE categories: cutaneous (0.745, 0.659 to 0.832), oral (0.734, 0.630 to 0.838), cardiovascular (0.675, 0.593 to 0.758), and gastrointestinal (GI, 0.742, 0.625 to 0.860), or 15 of 79 (19%) of PRO-CTCAE items related to adverse events including cutaneous (radiation burns, hypohidrosis, rash), oral (anorexia, dysphagia, dysgeusia), and GI symptoms (constipation, bloating), and others (anxiety, hoarseness, pain, erectile dysfunction). An exploratory analysis revealed that specific keywords linked to the PRO items were present in only one (11%) QLQ-C30 and 4 (5%) PRO-CTCAE items. Conclusions: The use of machine learning on clinical text predicts QOL and certain patient-reported adverse events with moderate accuracy in individuals undergoing intensive systemic treatment, suggesting its potential utility in syndromic monitoring where PRO is not formally assessed. Given many items cannot be accurately extracted, however, obtaining information directly from patients through questionnaires may still be required because of limited documentation by clinicians.
FcεRIγ-negative NK cells and association with improved outcomes in trastuzumab-treated patients.
Authors: Vincent Michael Perez, Sara R. Selitsky, Bin Yao, Austin Bigley, Sungjin Kim, Mark Walter Frohlich
Journal: Journal of Clinical Oncology (2023)

e12538 Background: A subset of natural killer cells lacking FcεRIγ expression (g-NK cells) demonstrate enhanced expansion, cytokine production, antibody-dependent cytotoxicity, and enhanced efficacy of therapeutic antibodies in preclinical models (Bigley, Blood Advances 2021). The monoclonal antibody, trastuzumab, is standard of care for treatment of HER2+ breast cancer in adjuvant and metastatic settings. We sought to determine whether the abundance of g-NK cells is associated with improved outcomes in trastuzumab-treated patients. Methods: We identified g-NK cells in single-cell (scRNA-seq) datasets from melanoma (n=47), renal (n=8), breast (n=29), and lung cancer (n=36) samples using predefined markers and defined a g-NK gene signature. We split the scRNA-seq cohorts into training and test sets and estimated cell-type compositions in pseudo bulk using MuSiC bulk tissue deconvolution (Wang, Nature Communications, 2019). We deconvoluted g-NK cells in 8 bulk RNA-seq HER2+ breast cancer cohorts (Table 1) and used Cox proportional hazard models to assess clinical outcomes stratified by g-NK and trastuzumab status. We reproduced our findings using real-world cohorts from patients sequenced via the Tempus xT test (Table 1). Results: The Spearman’s correlation coefficient between true and estimated pseudo bulk proportion of g-NK cells was 0.71 (p≤0.05). In a meta-analysis, the abundance of g-NK cells was associated with a lower hazard ratio (HR) for overall survival (OS) in trastuzumab-treated patients (cohorts 1-4; HR = 0.61; 95% CI, 0.37-0.99; p=0.04) but not trastuzumab-naive patients (cohorts 5-8; HR = 0.96; 95% CI, 0.80-1.15; p=0.65). In real-world, HER2+ breast cancer cohorts treated with trastuzumab, higher real-world progression-free survival (rwPFS) was associated with abundance of g-NK cells (N=104, HR = 0.78; 95% CI, 0.64-0.96; p=0.02). A similar trend was observed in real-world trastuzumab-treated gastric cancer patients (N=79, HR = 0.85; 95% CI, 0.72-1.00; p=0.06). Conclusions: G-NK cells are associated with improved OS and PFS in trastuzumab-treated patients from both clinical trials and real-world datasets, suggesting their presence may serve as a predictive marker for treatment efficacy. Adoptive transfer of g-NK cells is being explored to augment the efficacy of therapeutic monoclonal antibodies. [Table: see text]
The race, staging and clinical correlations with genetic mutations detected in breast cancer patients.
Authors: Nay Yee Wint Kyaw, Theresa Durana, Vijaya Natarajan, Yiqing Xu
Journal: Journal of Clinical Oncology (2023)

e12547 Background: Genetic testing has been applied widely in oncology and guidelines and criteria have been established for selection of testing. We aimed to study the variants of genetic mutations detected in a cohort of breast cancer patients of multiple ethnicity background, and its pathoclinical correlations. Methods: Breast cancer patients who have had a genetic test performed between 1/1/2010 until 1/31/2022 were eligible. Results: Among 767 patients tested, 77 patients were found to have germline mutations, including BRCA 1 (n = 20), BRCA 2 (n = 19), PALB2 (n = 12), CHEK 2 (n = 6), ATM (n = 4), RAD50 (n = 4), and others (n = 12). The race and ethnic groups were White/Caucasian (n = 23), African American (AA) (n = 25), Asian (n = 13), Jewish (n = 12) and Hispanic (n = 4). Genetic testing were performed when the tumors were diagnosed of stage 1-2 in 77.8% in white + jewish, 100% in Asian, 75% in Hispanic patients, but only 64% in AA patients. Non metastatic tumors with BRCA 1/2 mutation had a distribution in stage 1, 2, and 3 to be 30%, 37.5%, 27.5% respectively, while that for PALB2 was 0%, 83.3%, 8.3% respectively. BRCA 1 cancers showed 61.9% triple negative, 23.8% ER+/Her-2 neg, 14.3% ER-/Her-2 + distribution, and BRCA 2 cancers showed 31.6% triple negative, 63.2% ER+/Her-2 neg, and 5.3% ER+/Her-2 + distribution. PALB2 cancers showed 16.7% triple negative, 58.3% ER+/Her-2 neg, and 25% ER+/Her-2 + distribution. 4 (5.2%) patients were male, who had BRCA 2 (n = 2), RAD 50 (n = 1), and APC (n = 1), 3 were ER+/Her-2 neg, and 1 was ER+/Her-2 +. If NCCN criteria is used for selection for genetic testing, 8 (10.4%) patients will not meet the test criteria. Conclusions: Performance of genetic testing was done in more than 77% of the patient in early stage 1-2 breast cancer, which is significantly lower in AA subgroup (64%). BRCA 1/2 cancers presented in all early stages, while PALB2 cancers were predominantly stage 2 at diagnosis. Triple negative cancers were most common in BRCA 1, but can present in BRCA 2 and PALB2 mutations . RAD 50 and APC mutations can cause male breast cancer. Applying NCCN guideline, 10% patients will be missed for testing.
Differential responses to systemic therapy among patients who are financially fragile and receiving Medicaid: Results from ePRO and biometric monitoring study.
Authors: Scott David Ramsey, Kaiyue Yu, Veena Shankaran, Aasthaa Bansal, Karma L. Kreizenbeck, Morgan Glascock, Kate Watabayashi, Alejandra Benitez, Richa Wilson, Elaine Yu
Journal: Journal of Clinical Oncology (2023)

1527 Background: Cancer patients with Medicaid insurance have a 50% higher risk of unplanned ED admissions during systemic chemotherapy compared to commercially insured cancer patients. In a prospective study of an ePRO app and smartwatch to remotely monitor patients receiving anti-cancer therapy, we compared symptoms and biometric data among financially fragile (able vs. not to come up with $2000 in 30 days for an unexpected expense) Medicaid enrollees and commercially insured patients with solid tumor malignancies. Methods: The study was conducted at 3 community oncology practices in WA state. (ML41539, ISRCTN25569053) The ePRO had 15 common treatment-related symptoms from the PRO-CTCAE survey. 30 patients initiating systemic treatment wore a Samsung Galaxy 3 watch and completed the ePRO daily on study provided smartphones for 2 weeks. EPRO app adherence (ratio of completed to expected entries) was 91%. Smartwatch adherence (ratio of days with any biosensor data to number of days expected) was 86%. Composite symptom scores were calculated from ePRO responses using a published mapping algorithm (Range 0-3). Repeat symptoms, number of unique symptoms scores &gt;1, and average heart rate (HR) were compared. Results: Participants’ average age was 60 (68% female; 75% no comorbidity, 45% metastatic, 10% Medicaid, 13% reported financial fragility). Treatments: chemotherapy only (56%); immunotherapy only (11%); combination therapy (33%). Financially fragile patients had significantly higher average HR, unique symptoms, and repeat symptoms (e.g., &gt;1 day with symptoms). The average composite symptom score over 2 weeks was significantly higher for Medicaid enrollees, and trended higher for financially fragile patients. 16% of daily composite symptom scores recorded by Medicaid patients were 2 or greater, versus 7% for non-Medicaid patients (p&lt;0.001). Conclusions: Medicaid-insured and financially fragile patients may have more adverse responses to systemic therapy compared to more advantaged patients. If supported in larger studies, the findings may have profound implications for research aimed at improving clinical management in financially disadvantaged cancer patients.[Table: see text]
Efficacy comparison of anthracycline and taxane when added to immune checkpoint inhibitor in neoadjuvant chemotherapy of triple negative breast cancer: Clinical evidence from size-reduction measurement by ultrasound.
Authors: Shin-Cheh Chen, Shih-Che Shen, Chi-Chang Yu, Hsien-Kun Chang, Yung-Chang Lin, Jen-Shi Chen, Yun-Feng Lo, Wen-Lin Kuo, Hsiu-Pei Tsai, Hsu-Huan Chou, Chia-Hui Chu, Wen-Chi Shen, Ren-Chin Wu, Shir-Hwa Ueng, Yi-Ting Huang
Journal: Journal of Clinical Oncology (2023)

e12584 Background: Most chemotherapeutics can improve responses to immune checkpoint inhibitors (ICI) by increased immunogenicity. Anthracycline(AC), taxane(T) and platinum (CDDP) has most direct cytotoxic effect in neoadjuvant chemotherapy (NAC) of triple negative breast cancer (TNBC), but which one deserve the most immunostimulatory activity linked to their capacity of to kill cancer cell still unknown. Methods: A total of 91 patients with complete data of size measurement by ultrasound (US) were identified for the study from 363 consecutive TNBC patients received NAC between November 2010 to August 2022. They were divided into 3 groups. The 1st group patients received AC first, then T with CDDP, 2nd group in reverse sequence (T and CDDP first) and 3rd group, sequence as group 2 but adding ICI (pembrolizumab). Tumors size measured by US before chemotherapy, after 1st and after 2nd regimen of chemotherapy. Percentage of size reduction of tumor maximal diameter (cm), surface area (transverse x longitudinal diameter, cm 2 ) and volume (measured by 1/6 p x transverse x longitudinal x height cm 3 ) were calculated. Statistically significant was calculated using the Mann-Whitney U test for percentage of size reduction and Pearson's chi-squared test for pCR rate, p-value &lt; 0.05 was considered significant. Results: There were 14, 56 and 21 patients in group 1, 2 and 3, respectively. The significant difference of pathologic complete response rates 7.1%, 44.6% and 76.2% in each group as shown. The volume, surface area and maximal tumor size reduction percentage after 1st regimen chemotherapy in group 1 (AC), group 2 (T+CDDP) and group 3 (ICI+T+CDDP) were -67.24, -55.43, -31.13; -85.45, -72.13, -45.61 and -87.13, -69.75, -45.02, respectively, and size reduction after 2nd regimen chemotherapy in group 2 (AC) were, -42.19, -30.19, -21.13; and group 3 (ICI+AC) were -77.78, -50.76, -30.65; respectively. A statistical non-significant trend of greater size reduction in ICI+ AC than AC alone was found. Conclusions: The study is the first, direct evidence demonstrated the synergistic effect of size reduction after NAC for TNBC with AC and ICI, but not T. It supports the potential benefit of combining chemotherapy with immunotherapy such as Tonic trial reported. [Table: see text]
Social determinants of health and utilization of neoadjuvant chemotherapy in patients with triple negative breast cancer (TNBC) in the community oncology setting.
Authors: Michael A. Danso, Joseph Dye, Traci Leong, Robert Lawrence Reid, Angel Kidd, Janet L. Espirito, Nicholas J. Robert
Journal: Journal of Clinical Oncology (2023)

610 Background: TNBC has a higher incidence in African American women compared to European American, often presents at a younger age or more advanced stage, and is associated with worse outcomes. The use of multi-agent neoadjuvant chemotherapy (NC) improves event-free survival and overall survival in patients with early-stage TNBC and is considered standard of care. Race and other social determinants of health (SDOH) have been shown to affect outcomes in patients with TNBC. Differences in use of NC associated with SDOH may be a contributing factor to inferior outcomes. The aim of this study is to determine if SDOH measures affect utilization of NC in patients with early-stage TNBC. Methods: This retrospective observational cross-sectional study examined patient profiles, treatment patterns and SDOH indicators among patients newly diagnosed with early-stage breast cancer in The US Oncology Network. Using iKnowMed EHR data, patients diagnosed with TNBC between 03/31/2017 and 09/30/2021 with stages II-IIIB disease or tumor size ≥2cm (T2 or higher) were included. The initial TNBC diagnosis date was used as the index date for each patient and records were assessed from 6 months pre- to 6 months post-diagnosis for NC initiation, baseline characteristics, and social determinants, including Area Deprivation Index (ADI), a validated measure of socioeconomic status. Results: 3321 patients with TNBC were identified, with a mean age of 58 years; 59% were White, 15% Black, 3% Asian, and 23% other/unknown; and 2139 (64%) received NC. Patients who received NC relative to those who did not were younger (mean 55.9 vs 61.8; p=0.001), had higher BMIs (70% with BMI&gt;25 vs ≤25, p=0.045), and had commercial or Medicaid insurance (67.5% with commercial insurance or Medicaid vs. 52.5% with Medicare; p=0.001). Regional differences were observed, with proportionally fewer patients receiving neoadjuvant chemotherapy in the south US census regions and more in the west. There was no difference in NC use in Black vs White patients (66% vs 64%). No significant differences in receipt of NC were found for race, ethnicity, or ADI. Conclusions: In the community oncology setting, we did not observe inequities in the use of NC based on social determinants analyzed in this study, such as race, ethnicity, and ADI. Poorer outcomes observed in Black patients with TNBC may not be a result of underutilization of NC.
BRACELET-1 (PrE0113): Inducing an inflammatory phenotype in metastatic HR+/HER2- breast cancer with the oncolytic reovirus pelareorep in combination with paclitaxel and avelumab.
Authors: Amy Sanders Clark, Fengmin Zhao, Paula Klein, Alberto J. Montero, Carla Isadora Falkson, Elisa Krill-Jackson, Kendrith M. Rowland, Sagar D. Sardesai, Jason Anthony Incorvati, Patrick Michael Dillon, Antonio C. Wolff, Houra Loghmani, Richard Trauger, Thomas Charles Heineman, Matthew C. Coffey, Kathy Miller
Journal: Journal of Clinical Oncology (2023)

1012 Background: In preclinical studies, the oncolytic reovirus pelareorep promoted an inflammatory tumor microenvironment (TME) by promoting greater infiltration of tumor infiltrating lymphocytes and upregulating PD-1/PD-L1 expression, potentially increasing the efficacy of immune checkpoint blockade. The addition of pelareorep to paclitaxel (PTX) was associated with improved survival (10.4 vs. 17.4 mos., HR = 0.65, p = 0.1) in a prior trial, with the greatest benefit in patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease (N = 57; 10.8 vs. 21.0 mos., HR 0.60, p = 0.1). Methods: This is a randomized phase 2 study in pts with HR+/HER2- metastatic breast cancer. Patients must have progressed on at least one hormone therapy with a CDK4/6 inhibitor. After a safety run-in for Cohort 3, patients were randomized 1:1:1 to PTX-alone (Cohort 1), PTX + pelareorep (Cohort 2), or PTX + pelareorep + avelumab (Cohort 3). The primary endpoint was overall response rate (ORR) at week 16 according to RECIST v1.1 without formal comparison across groups. Toxicity, progression-free survival (PFS) and overall survival were secondary endpoints. Blood samples were collected at cycle 1-day 1 (C1D1), C2D1 and C4D1, and T-cell receptor sequencing was performed. Results: Forty-eight pts were enrolled between June 2020 and June 2022. Median age was 55.5 yrs, range 37-74. Forty pts (83%) had visceral disease. Six pts (12%) previously received everolimus, and 3 alpelisib. Thirteen pts (27%) received prior taxanes in the neo/adjuvant setting. Three pts who withdrew consent prior to starting therapy and 2 pts who discontinued treatment after week 1 were considered non-responders and were censored for PFS. The most common pelareorep-associated toxicities were fever, chills, and flu-like infusion reactions, which were occasionally severe enough to require hospitalization in 5 (15%) pts despite acetaminophen prophylaxis. Nine pts (33%) discontinued pelareorep and 6 (35%) discontinued avelumab due to toxicity. Pelareorep increased T-cell repertoire turnover, with identification and expansion of new and pre-existing T-cell clones by C2D1. Conclusions: The addition of pelareorep to PTX is an active regimen with a high 6-month PFS rate worthy of further study. One third of patients discontinued either pelareorep or avelumab due to toxicity, highlighting the need for attentive supportive care. Survival data is maturing. Clinical trial information: NCT04215146 . [Table: see text]
Association between patient-reported outcomes and therapeutic outcomes in patients with breast cancer: A pooled individual-participant data analysis.
Authors: Natansh Modi, Ahmad Y Abuhelwa, Andrew Rowland, Bradley D Menz, Ross Allan McKinnon, Michael J Sorich, Ashley Mark Hopkins
Journal: Journal of Clinical Oncology (2023)

530 Background: Patient-reported outcomes (PROs) are captured in validated tools to provide the patients’ perspective and voice on their physical, social, emotional, functional, and cognitive abilities. Pre-treatment PROs have shown prognostic importance in other cancer types, however, the prognostic value of PROs in breast cancer has been minimally explored. Methods: In a pooled analysis of contemporary clinical trial IPD from patients with breast cancer, cox-proportional hazard analysis and binary logistic regression was used to assess the association between potential predictors with overall survival (OS) and adverse event (grade ≥ 3) outcomes, respectively. PROs were recorded using the EORTC QLQ-C30 version 3.0 questionnaire in the pooled cohort. Statistical significance was set at a threshold of P&lt;0.05 and was determined via the likelihood ratio test. Model fit and linearity of variable associations were assessed via the Akaike information criterion (AIC). All analyses were stratified by age, performance status, treatment arm, and study. The primary assessed outcome was OS, with grade ≥ 3 adverse events assessed as a secondary outcome. A forward inclusion process (starting with the variable of lowest AIC, PRO domains were retained in the model if they decreased the AIC by 2 or more on addition, and remained statistically significant) was used to evaluate the value of multiple PRO domains on prognostic performances. Results: Within data available, the EORTC QLQ-C30 version 3.0 questionnaire was used in a pooled cohort of 8,544 patients across 8 clinicals trials. In the pooled cohort, the association between PROs and outcomes was best described by a linear association. Patient-reported physical functioning, appetite loss, and pain were significantly associated with OS. On forward-inclusion, only physical functioning remained within the OS prognostic model. Except for patient-reported financial difficulties, all PRO domains were significantly associated with grade ≥ 3 adverse events. On forward-inclusion, physical functioning, pain, and constipation all remained statistically significant. Conclusions: Within large high-quality IPD, pre-treatment PROs demonstrated significant prognostic relationships with therapeutic outcomes in patients with breast cancer initiating contemporary anticancer treatments. Patient-reported physical functioning was found to be the most prognostic PRO domain for OS, while patient-reported physical functioning, pain, and constipation were retained in a multivariable model prognostic of grade ≥ 3 adverse events.